Safety and Efficacy of Efavaleukin Alfa in Participants With Moderately to Severely Active Ulcerative Colitis

• ClinicalTrials.gov Identifier: NCT04987307
• Recruitment Status: Recruiting
• First Posted: August 3, 2021
• Last Update Posted: March 2, 2023
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: July 26, 2021
• First Posted Date: August 3, 2021
• Last Update Posted Date: March 2, 2023
• Actual Study Start Date: January 31, 2022
• Estimated Primary Completion Date: June 22, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 26, 2021): Number of Participants with Clinical Remission at Week 12 [ Time Frame: Week 12 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 26, 2021)

• Number of Participants with Clinical Response at Week 12 [ Time Frame: Week 12 ]
• Number of Participants with Endoscopic Remission at Week 12 [ Time Frame: Week 12 ]
• Number of Participants with Symptomatic Remission at Week 12 [ Time Frame: Week 12 ]
• Number of Participants with Combined Endoscopic Remission and Histologic Remission of the Colon Tissue at Week 12 [ Time Frame: Week 12 ]
• Number of Participants with a Clinically Significant Change from Baseline in Histological Score at Week 12 as Measured by Geboes Score [ Time Frame: Baseline to Week 12 ]
• Number of Participants who Experience One or More Treatment-emergent Adverse Events [ Time Frame: Up to 58 weeks ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Efavaleukin Alfa in Participants With Moderately to Severely Active Ulcerative Colitis
• Official Title: A Phase 2, Dose-finding, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of Efavaleukin Alfa Induction Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis

Brief Summary

The main purpose of this study is to evaluate the effect of efavaleukin alfa on induction of clinical remission in participants with moderately to severely active ulcerative colitis (UC).

Participants will be randomized to receive 1 of 3 efavaleukin alfa doses or placebo during a 12-week induction period. Participants who complete the 12-week induction period will have the option to enter an exploratory long-term treatment period for up to 40 weeks (total of up to 52 weeks of treatment) if, in the opinion of the investigator, they may benefit from continued treatment. During the long-term period, participants randomized to efavaleukin alfa will remain on the same efavaleukin alfa blinded dose; participants randomized to placebo who achieved clinical response at week 12 will remain on placebo; and placebo non-responders (ie, participants randomized to placebo who did not achieve clinical response at week 12) will receive efavaleukin alfa in a blinded manner during continued treatment. All participants will complete a safety follow-up visit 6 weeks after their last dose of investigational product.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Ulcerative Colitis

Intervention

• Drug: Efavaleukin alfa
  Efavaleukin alfa will be administered by subcutaneous (SC) injection.
  Other Name: AMG 592
• Drug: Placebo
  Placebo will be administered by SC injection.

Study Arms

• Experimental: Arm A: Efavaleukin alfa
  Efavaleukin alfa Dose 1 administered by SC injection once every two weeks (Q2W)
  Intervention: Drug: Efavaleukin alfa
• Experimental: Arm B: Efavaleukin alfa
  Efavaleukin alfa Dose 2 administered by SC injection Q2W
  Intervention: Drug: Efavaleukin alfa
• Experimental: Arm C: Efavaleukin alfa
  Efavaleukin alfa Dose 3 administered by SC injection Q2W
  Intervention: Drug: Efavaleukin alfa
• Placebo Comparator: Arm D: Placebo
  Placebo Q2W
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 26, 2021): 320
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 25, 2025
• Estimated Primary Completion Date: June 22, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Participant has provided informed consent prior to initiation of any study specific activities or procedures.
• Men and women aged ≥ 18 to < 80 years at screening visit (≥ 19 to < 80 in South Korea).
• Diagnosis of UC established ≥ 3 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report. If a histopathology report is not available at screening, then additional biopsies may be taken during the screening period for local histopathology analysis to corroborate.

• Moderately to severely active UC as defined by a modified Mayo score of 5 to 9, with a centrally read endoscopy subscore ≥ 2 and no subscore < 1 prior to day 1.

  • Participants require qualifying Mayo daily symptom diary subscores (a stool frequency subscore >=1 and rectal bleeding subscore >=1) to proceed to bowel preparation for screening endoscopy.

• Has documentation of:

  • A surveillance colonoscopy (performed according to local standard) within 12 months of day 1 visit for participants with pancolitis of > 8 years duration, or participants with left-sided colitis of > 12 years duration, or participants with primary sclerosing cholangitis.
  • At the discretion of the investigator, a colonoscopy (instead of a rectosigmoidoscopy) may be performed as the screening endoscopy for this study.
  • For all other participants, up-to-date colorectal cancer surveillance (performed according to local standard). Participants who do not have a colonoscopy report available in source documentation will have a colonoscopy instead of rectosigmoidoscopy performed as the screening endoscopy for the study.

• Participants must have demonstrated inadequate response, loss of response, or intolerance to at least 1 conventional therapy, biologic therapy, or targeted small molecule therapy (ie, Janus kinase [JAK]-inhibitor or or S1P modulators), as follows:

  1. Conventional therapy failed participants:

     • Corticosteroids (corticosteroid-refractory colitis, defined as signs and/or symptoms of active UC despite oral prednisone [or equivalent] at doses of at least 30 mg/day for a minimum of 2 weeks; or corticosteroid-dependent colitis, defined as: an inability to reduce corticosteroids below the equivalent of prednisone 10 mg/day within 3 months of starting corticosteroids without a return of signs and/or symptoms of active UC; or a relapse within 3 months of completing a course of corticosteroids).
     • History of intolerance of corticosteroids (including, but not limited to, Cushing's syndrome, osteopenia/ osteoporosis, hyperglycemia, or neuropsychiatric side-effects, including insomnia, associated with corticosteroid treatment).
     • Immunomodulators: signs and/or symptoms of persistently active disease despite at least 3 months treatment with one of the following at locally approved doses: oral azathioprine (eg, ≥ 1.5 mg/kg/day) or 6-mercaptopurine (eg, ≥ 0.75 mg/kg/day), or oral azathioprine or 6-mercatopurine within a therapeutic range as judged by thioguanine metabolite testing, or a combination of a thiopurine and allopurinol within a therapeutic range as judged by thioguanine metabolite testing.
     • History of intolerance to at least 1 immunomodulator (including but not limited to nausea/vomiting, abdominal pain, pancreatitis, liver function test abnormalities, and lymphopenia) and have neither failed nor demonstrated an intolerance to a biological medication (anti-tumor necrosis factor [TNF] antibody, anti-integrin antibody, or interleukin [IL]-12/23 antagonists) that is indicated for the treatment of UC.

  2. Biologic or targeted small molecule therapy failed participants: those who demonstrated inadequate response or loss of response or intolerance to biologic therapy for UC (eg, anti-TNF antibodies or IL-12/23 antagonists, anti-integrin antibodies) or targeted small molecules (eg, JAK inhibitors or S1P modulators). The therapy used to qualify the participant for entry into this category must be approved for the treatment of UC in the country of use, at the time of use. Participants must fulfil one of the following criteria:

     • Inadequate response: signs and symptoms of persistently active disease despite induction treatment at the approved induction dosing that was indicated in the product label at the time of use.
     • Loss of response: recurrence of signs and symptoms of active disease during approved maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not quality as having failed or being intolerant to UC biological therapy, JAK inhibitor, or S1P modulators).
     • Intolerance: history of intolerance to infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, tofacitinib or other approved biologicals, JAK inhibitors or S1P modulators (including but not limited to infusion-related event, demyelination, congestive heart failure, or any other drug-related adverse event that led to a reduction in dose or discontinuation of the medication).

• If receiving any of the following therapies, participants must have stable dosage for the specified duration:

  • 5-aminosalicylates (ASAs), stable dosage for ≥ 2 weeks prior to screening endoscopy.
  • Oral corticosteroids: prednisone ≤ 20 mg/day or its equivalent, stable dose for ≥ 2 weeks prior to screening endoscopy.
  • Budesonide: extended release tablets 9 mg/day [budensonide MMX], stable dose for ≥ 2 weeks prior to screening endoscopy.
  • Beclomethasone dipropionate: gastro-resistant prolonged-release tablet 5 mg/day, stable dose for >= 2 weeks prior to screening endoscopy.
  • Conventional immunomodulators: azathioprine, 6-mercaptopurine, methotrexate, stable dosage for ≥ 12 weeks prior to screening endoscopy.

Key Exclusion Criteria:

• Diagnosis of Crohn's disease, inflammatory bowel disease unclassified (indeterminate colitis), microscopic colitis, ischemic colitis, or clinical findings suggestive of Crohn's disease.
• Evidence of toxic megacolon, fulminant colitis, intra-abdominal abscess, or stricture/stenosis within the small bowel or colon.
• Participant has had extensive surgery for UC (for example, subtotal colectomy), or is likely to require surgery for the treatment of UC during the study.
• Currently receiving or had treatment within 12 months prior to screening with T cell depleting agents (eg, antithymocyte globulin, Campath).

• Participant has received any of the following prescribed medication or therapy within the specified time period:

  • Anti TNF antibodies (eg, infliximab, adalimumab, golimumab) < 8 weeks prior to screening rectosigmoidoscopy.
  • Anti integrin antibodies (eg, vedolizumab) < 8 weeks prior to screening rectosigmoidoscopy.
  • IL 12/23 antagonist (eg, ustekinumab) < 8 weeks prior to screening rectosigmoidoscopy.
  • JAK inhibitors (eg, tofacitinib) < 4 weeks prior to screening rectosigmoidoscopy.
  • Any other commercially approved biologic agent or targeted small molecule < 8 weeks prior to screening rectosigmoidoscopy or < 5 half lives prior to screening rectosigmoidoscopy, whichever is longer
  • Immunomodulatory medications, including oral cyclosporine, intravenous cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, thalidomide < 4 weeks prior to screening rectosigmoidoscopy.
  • Any investigational biologic therapy within 8 weeks prior to screening rectosigmoidoscopy or < 5 half-lives prior to screening rectosigmoidoscopy, whichever is longer.
  • Has used apheresis (eg, Adacolumnâ apheresis) < 2 weeks prior to screening rectosigmoidoscopy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Amgen Call Center; 866-572-6436; medinfo@amgen.com

• Listed Location Countries: Argentina, Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, Finland, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Spain, Switzerland, Taiwan, Turkey, United States

Administrative Information

• NCT Number: NCT04987307
• Other Study ID Numbers: 20170104; 2021-002537-41 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• URL: http://www.amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: March 2023